tbuckley/cabot-search huggingface dataset:
P748: IPSS-M PERFORMANCE IN PATIENTS WITH MYELODYSPLASTIC SYNDROME AT THE TIME OF HYPOMETHYLATING AGENT FAILURE
Authors: Samuel Urrutia, Kelly Chien, Ziyi LI, Alex Bataller, Emmanuel Almanza, Koji Sasaki, Guillermo Montalban-Bravo, Nicholas Short, Elias Jabbour, Tapan Kadia, Farhad Ravandi, Gautam Borthakur, Rashmi Kanagal-Shamanna, Carlos Bueso Ramos, Sherry Pierce, Hagop Kantarjian, Guillermo Garcia-Manero
Journal: HemaSphere (2023)

Background: The international prognostic scoring system (IPSS) for prognostication of outcomes in myelodysplastic syndrome (MDS) has been widely adopted. The IPSS-Molecular was recently developed to aggregate the value of specific genetic mutations, as these have shown to have an impact on prognosis. Aims: This study seeks to evaluate the performance of IPSS-M in MDS the setting of hypomethylating agent (HMA) failure. Methods: We reviewed patients diagnosed with MDS who progressed after HMA therapy in a single institution. Clinical, laboratory, cytogenetic, and molecular data was collected and annotated. IPSS-M was calculated and models calculating overall survival were created using the Kaplan-Meier survivor function. The c-index was calculated to evaluate for model predictive performance. Results: We identified 101 patients of which most were male (66%) with a median age of 72 years (IQR: 41-88). Median blast percentage was 4% (IQR: 0-18), 30% had complex karyotype, and the most frequent mutations were TP53 (19%), ASXL1 (14%), TET2 (14%), RUNX1 (13%), DNMT3A (10%), and SF3B1 (10%). Twenty-nine percent were treated with azacitidine, 26% with decitabine, 12% with HMA with immunotherapy combinations (12%), azacitidine + anti-CD47 therapy (5%) SGI-110 (8%), ASTX727 (7%), or azacitidine with venetoclax (4%), or decitabine with venetoclax (1%). All others (8%) were treated with HMA in combination with other agents. IPSS-M categories were 34%, 28%, 15%, 12%, 9%, and 1% for Very High, High, Moderate-High, Moderate-Low, and Very -Low, respectively. The c-index for this model was 0.62 (log-rank p=0.08). Summary/Conclusion: This study documents that IPSS-M is not accurate at risk stratifying patients with MDS at the time of HMA failure. Despite the inclusion of molecular variables and patient stratification, the risk of death may be too high to be adequately captured.Figure 1. Kaplan-Meier survival function for overall survival of patients with HMA failure by IPSS-M categories with p-value for log-rank test. Keywords: International prognostic index, Myeloid malignancies, Myelodysplastic syndrome, Hypomethylating agents
Conservative versus Liberal Oxygenation Targets in Intensive Care Unit Patients (ICONIC): A Randomized Clinical Trial
Authors: L. Imeen van der Wal, Chloe C. A. Grim, Michael R. del Prado, David J. van Westerloo, E. Christiaan Boerma, Hilda G. Rijnhart-de Jong, Auke C. Reidinga, Bert G. Loef, Pim L. J. van der Heiden, Marnix J. Sigtermans, Frederique Paulus, Alexander D. Cornet, Maurizio Loconte, F. Jeannette Schoonderbeek, Nicolette F. de Keizer, Ferishta Bakhshi-Raiez, Saskia Le Cessie, Ary Serpa Neto, Paolo Pelosi, Marcus J. Schultz, Hendrik J. F. Helmerhorst, Evert de Jonge, Jeanette Wigbers, Fabian Termorshuizen, Cintha Klop, Lilian Dawson, Yvonne Schriel-van den Berg, Els de Vreede, Jolanda Qualm, Matty Koopmans, Tim Krol, Martin Rinket, Wytze Vermeijden, Albertus Beishuizen, Jantine van Holten, Anissa Tsonas, Michela Botta, Tineke Winters, Janneke Horn, Denise Battaglini, Lorenzo Ball, Iole Brunetti
Journal: American Journal of Respiratory and Critical Care Medicine (2023)

Supplemental oxygen is widely administered to ICU patients, but appropriate oxygenation targets remain unclear.
PB1957: PROGNOSTIC SIGNIFICANCE OF CHRONIC LYMPHOCYTIC LEUKEMIA WITH IGHV-U IN THE ERA OF NOVEL AGNETS; REAL-LİFE DATA
Authors: Fatma Arikan, Pinar Ata, Senol Demir, Ozlem Yildirim, Özgür Mehtap, Atakan Erol, Bedrettin Orhan, Fahir Ozkalemkas, Meral Ulukoylu Menguc, Derya Demirtas, Ahmet Mert Yanik, Ozlem Candan, Tayfur Toptas, Ayse Tulin Tuglular
Journal: HemaSphere (2023)

Topic: 6. Chronic lymphocytic leukemia and related disorders - Clinical Background: Chronic lymphocytic leukemia (CLL) is the most common adult leukemia accounting for 25-30% of all the leukemias. It originates from a mature B cell with either mutated or unmutated immunoglobulin heavy chain variable region (IGHV) transcripts. A better understanding of the molecular basis and IGHV mutations status of CLL allows targeted therapies as a treatment options. Aims: We aim to present real-life data emphasizing the clinical features of our patients with immunoglobulin heavy chain variable region unmutated (IGHV -U) Methods: This multi-center, retrospective study included CLL patients with known IGHV mutational status. Ninety patients with available clinical data out of 114 patients who had IGHV mutation outcomes were included in our study. We evaluated IGHV mutation status by RNA-seq providing high resolution and high dynamic range transcription data. Results: The median age of the patients was 61 years(29-84), and 64.4% were male (Table 1). Forty-t wo patients (46.7%) had IGHV-U and 8 patients (8.9%) had both IGHV unmutated disease and 17p del. Fifty one patients 51 (56.7%) were treated during follow-up. Thirty-six percent of the patients received chemoimmunotherapy consisting of fludarabine, cyclophosphamide plus rituximab (FCR), or bendamustine plus rituximab (BR); 10% received chlorambucil in combination with anti CD20 antibodies or monotherapy; and 31% received Bruton’s tyrosine kinase inhibitor or B-cell lymphoma-2 (BCL-2) inhibitor with anti CD20 antibodies. In the treatment group 76.2 % IGHV unmutated disease and 62.5% of these patients were treated with novel agents. Median follow up time was 30.5 months (1-48). Median overall survival was 95.9% at 36 month in the cohort. Three-years OS for IGHV-M and IGHV-U was approximately 92.3 % and 100 %, respectively (p>0.5) (Figure1). No significant survival difference was detected in both groups during 36-months follow-up period.Summary/Conclusion: There were no difference in survival of patients with or without IGHV mutations. Our real life data suggested novel agents targeting B-cell receptor (BCR) pathway kinases or BCL-2 inhibitors can overcome the poor prognosis associated with unmutated IGHV status. Keywords: Immunoglobulin gene, Chronic lymphocytic leukemia
P1660: THROMBOSIS RISK IN PATIENTS WITH ACUTE LEUKEMIA (AL)
Authors: Binoy Yohannan, Frances Cervoni-Curet, Adan Rios
Journal: HemaSphere (2023)

Topic: 34. Thrombosis and vascular biology - Biology & Translational Research Background: Cancer significantly increases the risk of thrombotic events. Thrombosis can occur prior to a cancer diagnosis, be the initial manifestation, or develop during active oncologic therapy. Patients with acute leukemia (AL) have a significantly higher risk of developing thromboembolic events. Aims: The primary objective of this study was to determine the incidence of thrombotic events in patients with AL at our institution. Methods: We performed a single-center retrospective study of patients with AL admitted to Memorial Herman Hospital, Texas Medical Center from January 1, 2013 to December 31, 2022. We identified 161 consecutive adult patients with AL (acute lymphoblastic leukemia [ALL], n=26; acute promyelocytic leukemia [APL], n=35; and acute myeloid leukemia [AML], n=100). All patients with first or recurrent thrombotic events were recorded. Descriptive statistics was used to analyze the data. Results: Twenty-five of 161 patients (15.5%) had a thrombotic event: venous (n=19), arterial (n=4), or both arterial and venous thrombosis (n=2). The median age was 56 (range, 20–80) years. Thrombosis was the initial manifestation of AL in 14 patients (56%): 5 with APL and 9 with AML. Among 147 patients without thrombosis at diagnosis, 11 (7.4%) later had thrombotic events. The cumulative incidence of thrombosis in the first 6 months from diagnosis was 13.6%; 1 in ALL, 6 in APL, and 15 in AML patients. The most common site was central venous catheter–associated upper-extremity venous thrombosis (n=8, 32%). Pulmonary embolism occurred in 4 patients (16%): 3 with APL and 1 with AML. One patient each developed a hepatic vein thrombosis and right atrial thrombus. Arterial thrombosis occurred in 6 patients (3 each with AML and APL): 5 had a stroke and 1 had splenic and renal infarction (n=1). One patient died from stroke and intracerebral bleeding. Summary/Conclusion: Thrombosis can occur at diagnosis in APL and AML but is relatively rare in ALL. However, the later course of these illnesses have a similar risk of thrombosis; hence, appropriate risk mitigation strategies should be adopted. Keywords: Central venous catheter, Acute leukemia, Thromboembolic events
P1670: MICROPARTICAL-ASSOCIATED THROMBIN GENERATION IN PATIENTS AFTER MILD COVID-19
Authors: Olesia Matvienko, Natalia Silina, Olga Smirnova, Olga Golovina
Journal: HemaSphere (2023)

Topic: 34. Thrombosis and vascular biology - Biology & Translational Research Background: Now it is well known that coronavirus infection is associated with thrombosis complications. COVID-19 are accompanied by “cytokine storm”, cell activation and damage. It can lead to microparticles (MP) release. MP expresses tissue factor (TF) and procoagulant phospholipids on their surface that can enhance prothrombogenic potential. Patients after COVID-19 may have hypercoagulability and risk of thrombosis complication for a while. It is interesting to investigate the rolе of MP in sustenance of prothrombogenic changes after COVID-19 Aims: Estimation of MP significance for thrombin generation in patients after mild COVID-19 Methods: The study included 33 patients (median of age = 45) after mild COVID-19. Patients did not receive any antithrombotic prophylaxis with anticoagulant and/or antiaggregant medicines. Reference blood samples were obtained from 30 healthy people. Thrombin generation was measured in platelet-free plasma by Calibrated Automated Thrombinography (CAT) according to Hemker et al. Following triggers were used: «PRP-reagent», containing rTF (1pM), «MP-reagent», containing negatively charged phospholipids (4µM), with CTI (40 µ/ml). Following parameters were evaluated: endogenous thrombin potential (ETP, nM*min) and peak thrombin (Peak, nM). Data were described by non-parametric methods using the median (Me), Q1 – Q3 interval and Mann-Whitney U test (Statistica 12.0). P<0,05 was considered significant. Results: Results are presented in the table. Parameters of thrombin generation in the patient’s and control’s groups (Me, Q1 – Q3) - Parameters «PRP-Reagent» «MP-Reagent» Patients (N=33) Controls (N=30) Patients (N=33) Controls (N=30) ETP (nM·min) 562,5*428,3-918,6,0 471,8384,2-564,0 1263,4*721,8-1800,4 566,5453,2-708,0 Peak(nМ) 24,4*15,5-36,1 18,412,3-20,2 151,6*87,1-214,8 46,332,9-67,2 * - difference between patients and controls «PRP-reagent» and «MP-Reagent» allow to estimate thrombin generation which depends on procoagulant phospholipids and TF, respectively. Significant differences were found between patients and controls with both reagents but «MP-Reagent» revealed more considerable distinction between values of patients and healthy group. Summary/Conclusion: MP enhance thrombin generation and increase prothrombogenic potential of patients after mild COVID-19 because of TF and procoagulant phospholipids expressed on MP. Keywords: Coagulation, COVID-19, Microparticles
P398: HIGH-RISK CHILDHOOD AND ADOLESCENT AND YOUNG ADULTS ACUTE LYMPHOBLASTIC LEUKEMIA TREATED WITH THE EORTC 58951 PROTOCOL: RESULTS AND OUTCOME
Authors: Imen Frikha, Aicha Ben Kahla, Moez Medhaffer, Nour Louati, Imen Ben Amor, Rahma Mallek, Latifa Khalifa, Faten Kallel, Yossra Fakhfakh, Ikram Ben Amor, Moez Elloumi
Journal: HemaSphere (2023)

Background: More than 80% of children with acute lymphoblastic leukemia (ALL) can be cured, but subsets of patients have significantly worse outcomes. Improved supportive care and intensification of chemotherapy for the high-risk group of ALL have contributed to this improvement in survival rates. Aims: In this study, we analyzed the clinical, biological features, and therapeutic results of patients treated with the high-risk group of the EORTC 58951 pediatric protocol. Methods: From January 2000 to December 2021, 395 patients with ALL aged less than 30 years were treated by the EORTC 58951 pediatric protocol in the Hematologic department of Hedi Chaker Hospital. From those 37 patients were treated by the high-risk group (VHR). The VHR group includes patients with poor prednisone response at day 8 (more than 1000 blasts/mm3 on the blood smear), those with worse cytogenetic abnormalities (t (9,22), t (4,11), 11q23 deletion...), and those with complete remission after two courses of chemotherapy. From those patients, we analyzed the clinical and biological features (Age, sex, blood count, cytogenetic abnormalities, and blasts phenotypes) and therapeutic Results: remission rate, rate relapse, overall survival (OS), event-free survival (EFS) at 10 years follow up. Results: We enrolled 109 cases (27%) of ALL classified VHR groups. The median age of patients was 12 years old. Seventy-eight cases (72%) were aged under 15 years old. The sex ratio M/F was 1,8. Fifty-seven cases (52%) had T-ALL. A tumor syndrome was noted in 87 cases (83%). Hyperleukocytosis of more than 100 G/L was detected in 38 cases (35%). Oncologic karyotype revealed t(9,22) in 6 cases (6%), 11q23 deletion in 3 cases (3%), and t(4,11) in 3 cases (3%). On the 7th day of treatment with corticosteroids, 79% of cases were corticoresistant. The complete remission (CR) rate was 87% (95 cases). The rate of toxic death was 28%. Allogeneic bone marrow transplantation was performed in 30 of 95 patients with CR. Relapse occurred in 39 patients (38%). With a median follow-up of 140 months (11 years), OS and EFS at 10 years were both 41% versus 69% for other risk groups of ALL. Summary/Conclusion: Although the CR rate was 87%, OS and EFS were only 41% lower than those reported in the literature (80%). This could be explained by the higher rate of toxic death (28%) and the higher rate of relapse (38% versus 15 to 20% in the literature). Incorporating novel therapies, particularly immunotherapy (Blinatumumab, CAR T-cells) could improve the survival rates by decreasing the intensity of conventional chemotherapy and thereby reducing associated toxicity. Keywords: Children, High risk, Young adult, Acute lymphoblastic leukemia
PB1954: PROGNOSTIC ANALYSIS OF GENE MUTATIONS ON TIME-TO-FIRST TREATMEN IN 93 NEWLY DIAGNOSED CHRONIC LYMPHOBLASTIC LEUKEMIA PATIENTS
Authors: Xixi Xiang, Fu LI, Xiaojuan Deng, Jun Rao, Jiali LI, Sha Zhou, Hongyun Liu, Shijia Lin, Song Dong, XI Zhang
Journal: HemaSphere (2023)

Topic: 6. Chronic lymphocytic leukemia and related disorders - Clinical Background: Time-to-first treatment (TTFT) may be an important endpoint for treatment-naive chronic lymphocytic leukemia (CLL) patients since it can help to idntify early drives of disease. TTFT is not affected by treatment-induced clonal evolution, which reflects the intrinsic biology and disease heterogeneity better[1-3]. Aims: Prognostic analysis of gene mutations in newly diagnosed CLL patients who have a shorter TTFT, and tried to find more predictive driving genes in the early stage of the disease. Methods: We analyzed 93 patients newly diagnosed with CLL from January 2019 to December 2021 in the hematology medical center of the Xinqiao Hospital of Army Medical University. The data of 93 patients were randomly divided into test and train sets in a 2:1 ratio.We collected the clinical and laboratory characteristics of all patients. 72 CLL related genes were targeted sequenced based on next generation sequencing (NGS). The last follow-up time was from the time of statistical analysis by the investigator (December 2022). All genes were subjected to survival analysis to screen the genes that significantly affected TTFT in patients. Cox risk regression model was used to analysis of selected clinical and mutational factors were associated with TTFT. Use R-4.1.2 to make survival analysis and draw Kaplan-Meier curves. Results: The median age of 93 patients was 57.3 years (range 34~81 years), including 65 males (69.8%) and 28 females. There were 65 patients (69.9%) with IGHV mutated, and 5 patients with TP53 mutation. FISH detected 13 patients of del (11q) (16.1%), 5 patients of del (17p) (5.4%). With a median follow-up time of 27.0 months (95%CI 20.48-23.51) for all patients, 34 patients (36.56%) achieved TTFT. A total of 7 patients (7.53%) died, and of which two patients not reaching TTFT died from other causes (cardiovascular events and pulmonary infections) rather than disease progression. Four out of the 31 TTFT-24 patients appeared the transformation from Richter to Diffuse large B-cell lymphoma (DLBCL). Treatment free survival (TFS) of patients in the test set versus the train set was analyzed. EGR2, FBXW7 and RPS15 mutations were shown to be associated with shorter TFS. The relationships between the 10 univariate variables and the TFS were analyzed by Cox in the test set and train set, del (11q), EGR2, FBXW7, RPS15 (P<0.05) mutations were identified as poor prognostic factors. Multivariate regression analysis found that EGR2 (P=0.042 vs P=0.015) significantly influenced TFS in both sets, serving as an independent predictor of poor outcome for shorter TTFT. Summary/Conclusion: NGS played a significant role in TTFT prognostic analysis, with mutations in EGR2、FBXW7、RPS15 associated with shorter TTFT. EGR2 serves as an independent predictor of poor outcome. Keywords: Chronic lymphocytic leukemia
P968: ALLOCATION AND VALIDATION OF THE SECOND REVISION OF THE INTERNATIONAL STAGING SYSTEM IN THE ICARIA-MM AND IKEMA STUDIES
Authors: Aurore Perrot, Paul Richardson, Joseph Mikhael, Thomas G. Martin, Meral Beksac, Ivan Spicka, Marcelo Eduardo Capra, Mattia D’agostino, Pieter Sonneveld, Kamlesh Bisht, Taro Fukao, Rick Zhang, Keisuke Tada, Christina Tekle, Sandrine Macé, Zandra Klippel, Helgi van de Velde, Philippe Moreau
Journal: HemaSphere (2023)

Topic: 14. Myeloma and other monoclonal gammopathies - Clinical Background: The International Staging System (ISS) underwent revision to include high-risk chromosomal abnormalities (R-ISS), and recently, to assign a score for each risk feature, including 1q21+ (R2-ISS), providing better discrimination in patients (pts) with intermediate-risk multiple myeloma (MM) Aims: To validate R2-ISS in pts with relapsed/refractory MM (RRMM) and in pts treated with anti-CD38 monoclonal antibodies (mAb) using Phase 3 ICARIA-MM and IKEMA study data. Methods: Pts from the treatment (triplet) and control (doublet) arms were pooled for both the ICARIA-MM (isatuximab–pomalidomide–dexamethasone; Isa-Pd vs Pd) and IKEMA (Isa–carfilzomib–d; Isa-Kd vs Kd) studies. Pts were classified based on R2-ISS, where a score of 0 = Stage I; 0.5–1.0 = Stage 2; 1.5–2.5 is Stage3; and > 3.0 = Stage 4. Hazard ratios (HR) and corresponding confidence intervals (CI) were estimated using the Cox proportional hazards model. Results: Of 609 pts, 68 were classified as Stage 1; 136, Stage 2; 204, Stage 3; 55, Stage 4; and 146 were not classified. Progression-free survival (PFS) decreased with increasing stage (Stage 2, median [m]PFS 21.2 months [HR 1.52; 95% CI:0.979–2.358]; Stage 3, mPFS 12.2 months [HR 2.59; 95% CI: 1.709–3.923]; and Stage 4, mPFS 7.0 months [HR 3.51; 95% CI: 2.124–5.784] vs Stage 1, mPFS38.8 months). Pts receiving Isa-based triplet therapy had longer PFS vs those receiving doublet therapy (mPFS 23.9 vs 11.8 months [HR 0.544; 95% CI: 0.436–0.680]), which was seen for all R2-ISS stages (Table). In an exploratory overall survival (OS) analysis including final ICARIA-MM and immature IKEMA data, OS also decreased with increasing stage (Stage 2, mOS not reached [NR; HR 1.3;95% CI 0.78–2.18]; Stage 3, mOS 27.5 months [HR 2.77; 95% CI: 1.730–4.450]; and Stage 4, mOS 11.3 months [HR 4.25; 95% CI: 2.480–7.269] vs Stage 1, mOS NR). Summary/Conclusion: For the first time, these data independently validate the prognostic value of the R2-ISS staging system in pts with RRMM, and in pts treated with anti-CD38 mAb. Isa-based triplet therapy led to improved PFS regardless of R2-ISS stage vs the doublet.Keywords: Multiple myeloma, Chromosomal abnormality, CD38, Monoclonal antibody
P1520: PROGNOSTIC IMPACT OF FEBRILE NEUTROPENIA AND DOSE INTENSITY OF R-CHOP THERAPY IN PATIENTS WITH DIFFUSE LARGE B-CELL LYMPHOMA, A SUPPLEMENTARY ANALYSIS OF JCOG0601
Authors: Isao Yoshida, Ken Ohmachi, Naomi Konishi, Ryunosuke Machida, Dai Maruyama, Wataru Munakata, Tsutomu Kobayashi, Tomohiro Kinoshita, Kiyoshi Ando, Hirokazu Nagai
Journal: HemaSphere (2023)

Topic: 30. Infections in hematology (incl. supportive care/therapy) Background: Febrile neutropenia (FN) following chemotherapy is a potentially fatal complication, and subsequent treatment is often discontinued or reduced if FN occurs. A previous meta-analysis has demonstrated that reducing the dose of R-CHOP therapy less than the planned dose or prolonging the treatment interval implies a reduction in relative therapeutic intensity, resulting in poor treatment outcomes. In cases that developed FN after R-CHOP therapy but does not attenuate dose intensity (DI), the prognostic impact of FN has not been elucidated. Aims: We investigated whether the development of FN and relative DI (RDI) affect progression-free survival (PFS) and overall survival (OS) in JCOG0601 for untreated patients with diffuse large B-cell lymphoma. Methods: All eligible patients enrolled in JCOG0601 were included in the analysis (n=204 in arm A; 8 cycles CHOP-21 with 8 doses of rituximab once every 3 weeks and n=205 in arm B; 8 cylcles CHOP-21 with 8 doses of weekly rituximab). The entire cohort was divided into four groups according to the presence or absence of FN and RDI ≥ 85%. Group 1 (FN+, RDI of doxorubicin (DOX) or cyclophosphamide (CPA) < 85%) was used as the control arm for analysis with group 2 (FN+, RDI of DOX and CPA ≥ 85%), 3 (FN-, RDI of DOX or CPA < 85%), and 4 (FN-, RDI of DOX and CPA ≥ 85%). Results: RDI in arm A was CPA: 95.5% (range: 13.3-102.9%), DOX: 95.5% (range: 54.1-101.8%), and the RDI in arm B was CPA: 98.8% (range: 63.2-102.4%) and DOX: 98.8% (range: 62.5-102.4%). Forty-nine patients were classified in group 1, 67 in group 2, 27 in group 3, and 264 in group 4. There were no meaningful background differences among the four groups. The 5-year PFS were 73.5% (95% CI, 58.7-83.6%) in group 1, 80.6% (95% CI, 68.9-88.2%) in group 2, 61.0% (95% CI, 39.4-76.9%) in group 3, and 77.8% (95% CI, 72.2-82.5%) in group 4, respectively. The 5-year OS were 80.8% (95% CI, 66.2-89.5%) in group 1, 88.9% (95% CI, 78.0-94.6%) in group 2, 77.2% (95% CI, 56.0-89.1%) in group 3, and 86.1% (95% CI, 81.1-89.9%) in group 4, respectively. On univariable analysis, group 2 and group 4 had significantly better OS compared to group 1, while no significant difference was observed in PFS. There was no significant difference in groups 2, 3, and 4 compared to group 1 on multivariable analysis for PFS and OS. Summary/Conclusion: This study suggests that the attenuation of RDI rather than the presence of FN may have an impact on prognosis. Even in the presence of FN, the continuation of subsequent treatment without the attenuation of RDI may be associated with a better prognosis.Keywords: Febrile neutropenia, Cyclophosphamide, Doxorubicin, DLBCL